Health Update: Health Update: What is retatrutide? The experimental drug transforming weight loss – What Experts Say– What Experts Say.
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By now, very few people haven’t heard of Ozempic. Originally developed to treat type 2 diabetes by mimicking hormones that regulate blood sugar, the medication quickly became better known for its powerful impact on weight loss due to the way the same mimicking hormones affect appetite.
But while Ozempic is arguably the most recognizable drug in its class, it isn’t the only medication approved for weight management. Others include Wegovy and Saxenda, while newer drugs like tirzepatide (sold as Mounjaro and Zepbound) work through related hormonal pathways.
Now, additional drugs are generating even greater attention, with retatrutide dominating conversations and clinical trials alike, despite the medication not yet approved by the U.S. Food and Drug Administration (FDA). “Retatrutide is still under investigation, and long-term safety, dosing and side-effect profiles are still being evaluated,” says Dr. John Burns, a board-certified plastic surgeon and the president at Dallas Plastic Surgery Institute.
Here’s what researchers currently know about the drug, how it works and how it differs from existing weight management medications.
What is retatrutide?
Retatrutide is an experimental injectable weight-loss medication being developed by the pharmaceutical company Eli Lilly. “It is sometimes referred to as a ‘triple-agonist’ medication because it targets three key metabolic hormone receptors involved in appetite control and energy balance,” explains Burns.
Dr. Alison Mitzner, a board-certified physician based in New York City, says it has advanced through early- and mid-stage clinical trials and is currently being evaluated in large Phase 3 studies. This is typically the final stage of testing before a drug can be submitted for regulatory approval.
Interest in the drug surged after a 2023 clinical trial reported substantial weight loss among adults with obesity.
But researchers are also studying the drug’s effects on broader metabolic health, including blood sugar regulation, cholesterol levels and cardiovascular risk markers. That’s because obesity is closely linked to conditions such as type 2 diabetes, heart disease and fatty liver disease, so treatments that produce significant weight loss may also improve these related health risks.
How does retatrutide work? How is reatrutide different from Ozempic and Wegovy?
To understand retatrutide, it helps to look at how current medications function. Drugs like Ozempic and Wegovy contain semaglutide, which mimics a hormone called glucagon-like peptide-1, or GLP-1. Mitzner explains that this hormone is released after eating and “regulates blood sugar, slows digestion and signals fullness to the brain.” As a result, people taking these medications typically experience reduced hunger and therefore eat fewer calories.
Mitzner says that Mounjaro and Zepbound work by targeting two hormone receptors instead of one: GLP-1 and glucose-dependent insulinotropic polypeptide, or GIP. By influencing two metabolic pathways, both medications may similarly improve blood sugar control while also reducing appetite. “These drugs may also reduce nausea compared to GLP-1 medications alone,” says Burns.
Retatrutide works in a similar fashion but goes a step further by activating three receptors simultaneously: GLP-1, GIP and a receptor associated with glucagon. Affecting the first two receptors means retatrutide may help suppress appetite and slow digestion, which can help users feel full after eating even smaller meals. But its effect on glucagon is also noteworthy because that peptide hormone plays a role in how the body uses and burns calories for energy.
In simple terms, this triple-action approach may “address both sides of the weight-loss equation,” says Burns, by reducing how much you want to eat in the first place while also encouraging the body to burn more calories after you do.
So far, clinical trials suggest that people taking retatrutide may experience greater overall weight loss than what has been seen with earlier GLP-1 medications. Researchers have also observed promising improvements in metabolic markers and better preservation of lean muscle mass, says Burns.
But again, he and Mitzner stress that because retatrutide is still being studied, it’s not known how consistently these benefits occur or whether taking the medication remains safe over longer periods of use.
What is the best way to lose weight safely?
While medications like Ozempic and retatrutide will likely continue to generate excitement “and can be powerful tools,” says Burns, “they are not complete solutions on their own.”
He stresses that physical activity remains one of the most important components of long-term weight control. This is especially true of resistance training such as weightlifting because it helps preserve and build muscle that is commonly lost with any kind of weight loss – including weight loss associated with these medications. He adds that this also matters because muscle tissue plays a key role in metabolism and when people lose weight without maintaining muscle mass, the body can burn fewer calories at rest, “causing weight regain to become more likely.”
“Nutrition and eating habits matter significantly as well,” adds Mitzner, “not only for calorie awareness but also for increasing protein intake to preserve lean muscle and promote fullness.” She adds that eating whole foods and following a diet rich in lean meats, whole grains, legumes, fruits, vegetables and healthy fats is essential for ensuring the body receives vitamins, minerals and other nutrients.
Lifestyle factors also play a larger role than many people realize. Chronic sleep deprivation “can disrupt appetite hormones and increase cravings,” says Mitzner. Ongoing stress may have similar effects by elevating cortisol levels, a hormone associated with increased appetite and fat storage in some individuals.
Still, “medications like retatrutide represent an exciting evolution in medical weight loss,” says Burns, “but sustainable success comes from a comprehensive strategy” that includes nutrition, exercise and a healthy lifestyle.